Experiments are being conducted to determine the extent to which hypoxia affects acid-base regulation in extracellular fluid, cardiac muscle and skeletal muscle. Adult male rats are bilaterally nephrectomized and the carotid artery cannulated. The radionucleides, H-3 Inulin and C-14 DMO are administered for measurement of extracellular fluid volume and determination of all pH respectively. The animals are then allowed to breath the desired gas mixture for two or four hours. An arterial blood sample is obtained, the animal anesthetized and the heart and gastrocnemius muscle removed. Blood gas analysis, pH measurement and cellular pH determination are carried out using established methods. Under normoxic conditions, arterial pO2 equal 86 minus 103 torr, the production of hypercapnia arterial pCO2 equal 70 minus 74 torr resulted in significant decreases in myocardial and skeletal muscle pH. Under hypoxic conditions, arterial pO2 equal 45 minus 54 torr, a similar increase in arterial pCO2 resulted in decreases in myocardial and skeletal muscle pH. However, in some conditions, the decreases in cell pH were less than those observed in normoxic animals.